Homozygous (Hom) JAK2V617F expression induces severe erythrocytosis in JAK2^R/R knock-in mice. (A) JAK2^R/R mice show strikingly increased Hb, lower platelet levels (relative to JAK2^R/+), but normal white blood cell counts. Peripheral blood was collected from 6- to 8-week-old WT, JAK2^R/+, and JAK2^R/R mice. Significant differences are indicated and were determined using a linear mixed-effect model to accommodate the longitudinal and grouped data structure. (B) New methylene blue staining of peripheral blood showing increased numbers of reticulocytes (as indicated by arrows) in JAK2^R/R mice. (C) Increased number of reticulocytes in JAK2^R/R mice compared with WT and JAK2^R/+ as shown by increased number of CD71⁺Mitotracker⁺ erythrocytes. (D) Spleen size was significantly increased in 8-week-old JAK2^R/R mice. Asterisks indicate significant differences as determined by Student t test (*P < .05). Data are shown as mean ± standard error of the mean (SEM). BM (E) and spleen (F) sections stained with hematoxylin and eosin (H&E), examined using ×40 and ×4 objective lenses, respectively. (G) Spleen sections stained with Perls’ stain for iron. Het, heterozygosity.